Category Archives: Ali’s Diabetes Course

Majid Ali, M.D.

New York  212-873-2444

New Jersey . 201-996-0027


 

Unless specified otherwise,

the word at this web site is used for Type 2 diabetes.


 

BEWARE!

  1. If you think, diabetes is a sugar problem, tests done for blood sugar levels for screening for diabetes will be misleading most of the time.
  2. The diagnosis of diabetes will be delayed for five, ten, or more years.
  3. If you are overweight, it will be much more difficult to lose weight. 
  4. Unless you are at your optimal weight, undetected insulin toxicity will injure all your body organs to varying degrees until diabetes is diagnosed and treated for years, usually five to ten or more years.

 

References for Insulin Toxicity and Diabetes 

  1. Ali M. Fayemi AO, Ali O, Dasoju S, et al. Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes. Townsend Letter. 2017; 402:91-96.
  2. Ali M. Importance of Subtyping Type 2 Diabetes Into Subtype A and Subtype 2A and Subtype 2B.  Townsend Letter. 2014; 369:56-58.
  3. Ali M, Dasoju S, Karim N, et al. Study of responses to carbhydrate and non-carbohydratechallenges in insulin-based care of metabolic disorders. Townsend Letter. 2016; 391: 48-51.

 

What IS Insulin Toxicity

Blood insulin test should be done for the following conditions since there is high probability that the underlying fires of these conditions are fed by insulin toxicity.

 

·       Loss of Vigor

·       Weight gain

·       Course skin

·       Acne in teenager

        Skin pigmentation changes

·       Facial hour for young women

·       Tingling and numbness in toes and fingers

·       Brain fog

·       Cognitive difficulties

·       Memory loss

·       Any infections that do not heal

·       Any inflammation that does not heal

·       Colitis of immune-inflammatory disorders

·       Arthritis of immune-inflammatory disorders

·       Connective tissue diseases

·       Any skin conditions that do not heal

·       Neurodermatitis

·       Brain atrophy

·       Brain degenerative conditions

·       Rising blood creatinine level

·       Rising liver enzyme levels

·       Rising CRP test results

·       Liver ultrasound with fatty liver disease, steatosis, or steatonecrosis.


 

Blood Cells Tell The Insulin Toxicity Story

Healthy Blood Cells for Comparative Study. Figure 1

Early Stress on Red Blood Cells (lower picture) . Figure 2


Red Blood Cells in a Micro-clot In Uncontrolled Diabetes (upper Picture) Figure 3

Red Blood Cell Clot Breaking Up (lower Picture) Figure 4


Micro-plaque Formation In Uncontrolled Diabetes (both pictures) Figures 5-6


 

Figure 7 (top) illustrates severely damaged erythrocytes in a 52-year-old man with persistent atrial fibrillation. Close examination shows some zones of congealing surrounding many damaged red blood cells.

Figure 8 (bottom) illustrates a zone of plasma congealing unaccompanied by any cellular elements of the blood (seemingly a “spontaneous” phenomenon) in a diabetic with IHD. In our view, such congealing represents accelerated oxidative stress on plasma.


 

Figure 9 (top) shows some needle-like and amorphous granular microclots in a patient with unstable angina.

Figure 10 (bottom) shows a “dirty” blood smear of a man with severe peripheral vascular disease and extensive bilateral leg ulcerations, showing zones of plasma congealing and lumpiness, platelet clumping, and some other zones of plasma congealing unaccompanied by any blood corpuscular elements, representing diffuse changes of AA oxidopathy.


 

Figure 11 (top) shows a microclot formed by a large aggregate of platelets and congealed plasma in a patient five days after angioplasty.

Figure 12 (bottom) shows another field from the same smear and illustrates how microclots in oxidative coagulopathy grow in size when oxidative stress persists.


 

Figure 13 (top) and figure 14 (bottom) show two microplaques in a patient who had received three unsuccessful angioplasties for advanced IHD. Photomicrographs were taken the day after a major nosebleed. Note the compaction of necrotic debris and blood elements in microplaques as contrasted with loose structure of microclots in figure 11.

 


References for Oxygen, Inflammation, Insulin, and Diverse Diseases

 

1.    Ali M. Spontaneity of Oxidation in Nature and Aging, (monograph). Teaneck, NJ, 1983.

2.    Ali M. Leaky Cell Membrane Disorder (monograph). Teaneck, NJ, 1987.

3.    Ali M. The agony and death of a cell. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine. Denver, Colorado, 1985.

4.    Ali M. Molecular medicine. In: The Cortical Monkey and Healing. Institute of Preventive Medicine, Bloomfield, NJ, 1990.

5.    Ali M. Ascorbic acid reverses abnormal erythrocyte morphology in chronic fatigue syndrome, Am J Clin Pathol. I990;94:5I5.

6.    Ali M. Ascorbic acid prevents platelet aggregations by norepinephrinc, collagen, ADP and ristocetin. Am J Clin Pathol 1991;95:281.

7.    Ali M. The basic equation of life. In: The Butterfly and Life Span Nutrition. The Institute of Preventive Medicine Press, Denville, New Jersey. pp 225-236, 1992,

8.    Ali M. Oxidative theory of cell membrane and plasma damage. In Rats, Drugs and Assumptions. 1995. Life Span, Denville, New Jersey. pp 281-302, 1995.

9.    Ali M, Ali O. AA oxidopathy: the core pathogenetic mechanism of ischemic heart disease. J Integrative Medicine 1997;1:1-112.

10.  Ali M. Ali O. Oxidative coagulopathy in fibromyalgia and chronic fatigue syndrome. Am J Clin Pathol 1999; 112:566-7.

11.  Ali M, Ali O. Fibromyalgia: An oxidative-dysoxygenative disorder (ODD) J Integrative Medicine, 1999;1:1717.

12.  Ali M. Syllabus of capital University of Integrative Medicine, 1997 Washington, DC.

13.  Ali M. Oxidative regression to primordial cellular ecology (ORPEC): Evidence for the hypothesis and its clinical significance. J Integrative Medicine 1988;2:4-55.

14.  Ali M. Primacy of the erythrocyte in vascular ecology. J Integrative Medicine. 2000;3:5-18.

15.  Ali M. The Oxidative-dysoxygenative perspective of apoptosis. J Integ Medicine. 2000;4:5-45.

16.  Ali M, Ali 0, Fayemi A, et al: Improved myocardial perfusion in patients with advanced ischemic heart disease with an integrative management program including EDTA chelation therapy. J Integrative Medicine. 1997;1:113-145.

17.  Ali M: Hypothesis: Chronic fatigue is a state of accelerated oxidative molecular injury. J Advancement in Medicine, 1993;6:83-96.

18.  Efficacy of ecologic-integrative management protocols for reversal of fibromyalgia: an open prospective study of 150 patients. J Integrative Med 1999:3:48-64.

19.  Ali M. Oxidative coagulopathy In environmental illness. Environmental Management and Health. 2000;11:175-191.

20.  All Recent advances in integrative allergy care. Current Opinion in Otolaryngology & Head and Neck Surgery 2000:8:260-266.

21.  Ali M. The agony and death of a cell. Syllabus of the instructional course of the American Academy of Environmental Medicine Denver, Co. 1985.

22.  Ali M. Intravenous Nutrient protocols in Nutritional Medicine, (monograph). Institute of Preventive Medicine. Denville, New Jersey 1991.

23.  Ali M. Oxidative theory of cancer. In: Rats, Drugs and Assumptions. 1995. Life Span, Denville, New Jersey. pp 1995:281-302

24.  Ali M. Amenorrhea, oligomenorrhea, and polymenorrhea in CFS and fibromyalgia are caused by oxidative menstrual dysfunction. J Integrative Medicine 1998;3:101-124.

25.  Ali M, Ali 0, Fayemi A, et al: Efficacy of an integrative program including intravenous and intramuscular nutrient therapies for arrested growth. J Integrative Medicine 1998:2:56-69.

26.  Ali M. Oxidative theory of cell membrane and plasma damage. In: Rats, Drugs and Assumptions. Life Span, Denville, New Jersey, 1995:281-302.

27.  Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine l999;1:11-16

28.  Ali M. Darwin, Oxidosis, Dysoxygenosis, and Integration. J Integrative Medicine. 1999;3:11-16.


 

The Diabetes Question

Majid Ali, M.D.

Does Diabetes Begin As a Rising Blood Sugar Disease Or As a Rising blood Insulin Disease?

We Will Let Call It  

The Diabetes Question.


If the answer to the diabetes question is that it begins with rising blood insulin levels,  not with rising blood glucose levels, then the following new questions arise?

Question: Is excess insulin (hyperinsulinism) toxic to the body organs?

Answer, Yes, Excess insulin is fattening, fermentiing, and inflaming. It swells the liver and shrinks the brain. It is pro-cancer, pro-inflammation, and pro-degenerative diseases. In damages endo cells which lines the inside of the entire cardiovascular system and affects blood circulation everywhere in the body. Simply stated, excess insulin (insulin toxicity) is “pro-accelerated pro-aging.” 

Question: Can insulin toxicity be assessed with blood sugar tests?

Answer. No.

Question: In most people, how long does insulin toxicity go on undetected before blood sugar levels rise enough to make diabetes diagnosable with blood sugar tests?

Answer, for five, ten, or more years?

Question: Do doctors usually always test for blood insulin level before they test for blood sugar level?

Answer, No.


 

What Must Be Known About Crucial Diabetes and Its Complications

(In this article the terms diabetes and Type 2 dabetes are used interchangeably)

Diabetes (Type 2 Diabetes,T2D) Cannot Be Diagnosed In Time Without Insulin Tests, Diabetes Cannot Be Reversed Without Insulin Intelligence. Nor Can Diabetes Complications Be Prevented or Reversed Without Insulin Intelligence.


 

Summary

Diabetes Is Not a Sugar Problem,

It Is a Problem of Insulin Toxicity (Hyperinsulinism).

Insulin Toxicity Predates Diabetes by Five, Ten, or more Years, and Directly Leads to the Disease.


 

The Cost of Neglected Insulin Testing 

Hyperinsulinism (insulin toxicity) inflicts cellular injury in nearly all cellular populations in the body.  During the  years insulin toxicity remains ,undetected and untreated, simply because insulin testing is neglected by practitioners. Why?

Blood insulin testing is not considered a standard of care by those who control $1.3 trillion yearly spending for medical care in the United States. After considering the evidence I present in this and other articles in my “Diabetes Question Series,” the readers will decide for themselves as to the real reason for neglected insulin testing.  

I Leave the answer to readers.    


What Is Insulin Intelligence?

Simply stated, excess insulin (insulin toxicity and hyperinsulinism by other names)  is a fire which burns all parts of the body. It may start in different places and spread differently but the end result is always shortened life span with different diseases.

A practitioner who answers this questions with the “diabetes-hyperinsulinism” prevailing view does not, in my opinion, serve his patients well. Anyone who answers the question with one-liners recognizing insulin as the “life-span” hormone without does not deserve anyone’s time. As for me, I want to invite you to consider these questions by taking my free-of-cost course at this web site. A library of my selected article, published papers, and short videos is included in this post. Readers interested in my book on reversing diabetes and video seminar downloads can access these materials at http://www.aliacademy.org.


 

The Diabetes Question:

Can insulin regulation be assesses with sugar tests?

Specifically, can diabetes be detected in time with fasting blood sugar test, A1c blood tests, two-hour post prandial (after a meal) blood sugar level?

The answer: Categorically not.


 

What Is Optimal Insulin Homeostasis?

First, when the blood insulin levels after a glucose challenge are quite low;

Second, blood glucose after a glucose challenge are within low physiologic range.

Third, when there is no history of diabetes in parents and grandparents.

Fourth, when there is no insulin toxicity.

Fifth, when the immune system is robust and there is no chronic . immune-inflammatory disease.

Question: Can one optimize one’s insulin homeostasis? One can only answer this question for oneself.


 

One can tell oneself lies, but nature does not grant permission to believe one’s own lies. 


Can insulin homeostasis (insulin regulation as a whole) be assessed with blood sugar tolerance  test, A1c blood tests, two-hour post prandial (after a meal) blood glucose tests, as for instance the tolerance test done for gestational diabetes?

The answer: Categorically not.


To provide a broader context for due deliberation of the above questions, please consider sets of blood insulin and glucose profiles below which were prepared with fasting and timed post-glucose challenge.
       Table  1  Control Profiles
       Table 2,3 Blood glicose tests are inappropriate for assessing insulin homestasis
       Table 4.  Hyperinsulinism in Autism Spectrum Disorder 

Table 1. Two Sets of Control Insulin and Glucose Profiles

1.Healthy control subject:. Case 1.

                 INSULIN :    <2 uIU/mL, 18, uIU/mL, 4,       and <2;    

                 GLUCOSE:    77, 168, 109, 74, 52.

2. Healthy Control Subject: Case 2  

               INSULIN :    3 uIU/mL, 11, uIU/mL, 7,   and <2;    

               GLUCOSE:    81  157, 98, 63, 52.


The Challenge in Reversing Diabetes

is not to know what any doctor thinks about diabetes and drugs used to treat diabetes but how to learn to think for yourself about insulin, health, and healing.

I suggest you spend time at http://www.alidiabetes.org 


The Most Important Question in the Prevention and Reversal of Diabetes (Type 2)

No question is more important for stemming the global tides of insulin toxicity and diabetes than the question in the title of this post.


The Answer:

Insulin levels rise first, usually by five, ten, or more years before blood sugars level rise.
Why is this important?
Because insulin toxicity continues to cause cellular damage in the liver, kidneys, heart, brain, eyes and other organs unknown to the patient and the doctor if insulin tests are not done. For more info, go to http://www.Ali Diabetes.Org for the author’s free-access course at
http://www.Ali Diabetes.Org.

https://wordpress.com/post/alidiabetes.org/2966


Table 2. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes
Insulin Category*
Percentage of Subgroup
Mean Peak Glucose  mg/dL
(mmol/mL)
Mean Peak Insulin (uIU/mL)
Exceptional Insulin Homeostasis.N 12**
1.7%
110.2     (6.12)
14.3
Optimal Insulin Homeostasis N =126
24.9 %
121.2     (6.73)
26.7
Hyperinsulinism, Mild                N =197
38.9 %
136.5   (7.58)
58.5
Hyperinsulinism,  Moderate       N =134
26.5 %
147.0    (8.16)
109.1
Hyperinsulinism,  Severe             N =  49
9.7 %
150.0    (8.33)
(less than time and a half higher) 
231.0
(nearly 17 times higher)
#   Correlation coefficient, r value, for means of peak glucose and insulin levels in the five insulin categories is 0.84.
  *Criteria for classification: (1) Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis with fasting insulin concentration of <2 uIU/mL and mean peak insulin concentration of <20; (2) optimal insulin homeostasis, peak insulin <40 accompanied by unimpaired glucose tolerance; (3) mild insulin homeostasis, peak insulin  between <40 and 80 uU/mL;  accompanied by unimpaired glucose tolerance; ; (3) moderate insulin homeostasis, peak insulin  between <80 uU/mL and 160 uIU/mL accompanied by unimpaired glucose tolerance;  and (4) severe insulin homeostasis, peak insulin  > 160 uU/mL accompanied by unimpaired glucose tolerance.

Why Do Diabetics Need Insulin Shots?

Because Their Pancreas Has Exhausted Its Lifetime Capacity of Produce Sufficient Insulin

Note the extremely high blood insulin level (298 uIU/mL) still cannot keep the blood glucose level in the normal non-diabetic level.
Table 3. Insulin Homeostasis Categories in 178 Study Subjects With Type 2 Diabetes.
Insulin Category
Percentage of Subgroup
Mean Peak Glucose, mg/dL
(mmol/mL)
Mean Peak Insulin (uIU/mL)
Diabetic Hyperinsulinism, Mild              N =  53
29.0%
252.0   (14.00)
55.4
Diabetic Hyperinsulinism, Moderate    N =  42
24.0%
242.1   (13.45)
112.4
Diabetic Hyperinsulinism, Severe          N =  24
13.9%
224.6   (12.47)
298.0
Diabetic  Insulin Deficit                             N =  59
33.1%
294.0    (16.33)
22.9

What Is Optimal Insulin Homeostasis?

It is the lowest blood insulin levels that can keep the blood glucose levels in the normal range.
In other words, It is ideal state of insulin utilization, in which insulin toxicity does not exist, nor is insulin wasted because there is too much of it in the blood.
is not wasted .
In 2017, in a large survey of insulin and glucose profiles in the general New York metropolitan population, my colleagues and I reported a hyperinsulinism prevalence of 75.1%. Below is the link to get free access to the full text of this report:

http://www.townsendletter.com/Jan2017/insulin0117.html

Or, you may get the report on this website by entering , please use the the following words on the search box of the site:  “Shifting Focus from Glycemic Status.”

Examples of Insulin and Glucose Profiles of Individuals With Perfect Insulin Regulation

Table 1. Post-Glucose Load Insulin and Glucose Profiles of Seven Individuals With Optimal Insulin Homeostasis as Defined Above.
Fasting
½-Hr
1-Hr
2-Hr
3-hr
Insulin Profile 1. Insulin And Glucose Profiles of a 47-yr-old 5′ 5″ Male Runner Weighing 130 lbs. Who Presented With Inhalant Allergy and Hemorrhoids.
Insulin uIU/mL
1.5
9.7
9.0
4.6
<1.0
Glucose mg/dL
72
148
134
108
54
Insulin Profile 2. Insulin and Glucose Profiles of a  45-Yr-Old  5’9″Man Weighing 125 lbs. Presenting With Allergy and Dry Skin.
Insulin uIU/mL
1.0
2.7
9.8
2.7
<1.0
Glucose mg/dL
85
110
75
70
52
Insulin Profile 3. Insulin and Glucose Profiles of a 51-year-old 5’6″ Man Weighing 120 lbs. He Consulted Me for Cardiac Rhythm Disorder, Hypothyroidism and  Allergy.
Insulin uIU/mL
2.9
6.0
11.5
2.5
Glucose mg/dL
89
103
134
110
59
Insulin Profile 4. Insulin and Glucose Profiles of a 52-Yr-Old 5’1″ Woman Weighing 120 lbs. Presenting With Constipation and  Allergy.
Insulin uIU/mL
<2
17
15
6
Glucose mg/dL
78
61
72
71
Insulin Profile 5. Insulin and Glucose Profiles of a  52-Yr-Old 5’ 7″ Man Weighing 155 lbs. Presenting With Anxiety, Depression, and Diarrhea. A1c. 5.3%
Insulin uIU/mL
2.0
8.1
19.6
17.7
4
Glucose mg/dL
94
140
158
91
73
Insulin Profile 6. Insulin and Glucose Profiles of a  62-Yr-Old  5’3″ Woman Weighing 114 lbs. Presenting With Allergy and Hand Arthralgia.
Insulin uIU/mL
1.8
17.8
11.0
10.0
Glucose mg/dL
80
159
76
75
68
Insulin Profile 7. Insulin and Glucose Profiles of a 51-year-old 5’2″ Woman Weighing 120 lbs. She Consulted Me for Hypothyroidism and  Allergy
Insulin uIU/mL
3.2
11.8
2.4
1.9
Glucose mg/dL
86
110
75
70
52
Insulin Lab Reference Ranges Not  Fit for Use
In a previous report the author and his colleagues have highlighted the serious problem of inappropriate prevailing reference ranges for blood insulin concentrations.13 The data in Table 2 reproduced from that publication dramatically illustrates the dimension of this problem with findings of a survey of major laboratories in the New York City metropolitan area. The study data also calls into question the clinical value of single and random blood insulin test results. Photographs of illustrative lab reports are posted online.14

Absurd Laboratory Reference Ranges

Table 2. Upper and Lower Limits of Laboratory Insulin Reference  Ranges Expressed In uIU/mL Following a Standard Glucose Load From Six Major Clinical Laboratories in the New York Metropolitan Area.2
Laboratory
Fasting
1 Hr
2 Hr
3 Hr
Laboratory 1
1.9 – 23
8  –  112
5 – 35
Laboratory  2
2.6 – 24.9
0.0  – 121.9
0.0 – 163.5
Laboratory  3
2.6 – 24.9
8  –  112
5  –  55
3  –  20
Laboratory  4
6  – 27
20  –  120
18  –  56
8  –  22
Laboratory  5
00  – 30
30  –  200
40  – 300
50  – 150
Laboratory  6
Does not include insulin ranges in the report. Instead it includes the following note: Insulin analogues may demonstrate non-linear cross-reactivity in this essay. Interpret results accordingly. Personal communications with clinicians revealed that they do not find this laboratory note to be helpful.
 
 

Spectrum of Insulin Dysfunction and Hyperinsulinism in Autism

Table 4 presents insulin and glucose profiles of 10 patients with dysautonomia. Note that all patients suffered from allergic disorders.
Table 4. Insulin and Glucose Profiles of Individuals With Autism.
The Blood Insulin and Glucose Levels Are Expressed in uIU/mL and mg/dL respectively.
Fasting
½ Hr
1 Hr
2 Hr
3 Hr
Autism Case 1. Insulin and Glucose Profiles of 14-Yr-Old 5’ 9” Boy Weighing 115 lbs.Who Presented Without Expressive Speech Since Birth.
Insulin uIU/mL
24
300
235
211
83
Glucose mg/dL
83
129
98
95
61
Autism Case 2. Insulin Profile and Glucose Profiles of 15-Yr-Old Boy With  Autism, Allergy, and Fatigue.
Insulin uIU/mL
10.4
43.7
37.6
33.7
7.8
Glucose mg/dL
79
104
86
82
53
Autism Case 3. Insulin and Glucose Profiles of 17-Yr-Old-Boy With Autism, Eczema, And Anxiety.
Insulin uIU/mL
24.4
N/A
73.8
71.6
28.0
Glucose mg/dL
95
N/A
79
79
69
Autism Case 4.  Insulin and Glucose Profiles of 8-Yr-Old Boy Presenting With Autism, Sudden Mood Shifts, and Inhalant Allergy.
Insulin uIU/mL
6.2
40.36
41.5
24.8
3.9
Glucose mg/dL
96
192
131
109
57
Autism Case 5. Insulin and Glucose Profiles of A Three-Year-Old  Boy With Asperger’s Syndrome, Temper Tantrums, Eczema, And Inhalant Allergy.
Insulin uIU/mL
1.28
14.3
0.33
Glucose mg/dL
71
126
88
Autism Case  6. Insulin and Glucose Profiles Of A Four-Year-Old Boy Weighing 35 lbs. Limited expressive speech, Often in non-communicative trance. Mother’s Words: “Very Intelligent In Things That Interest Him.”
Insulin uIU/mL
2.3
24.2
20.2
17.8
0.8
Glucose mg/dL
89
151
102
98
79
Autism Case 7 .  Insulin and Glucose Profiles of A 5-yr-old Boy With Autism Focus Disorder. No Expressive Speech Until Age 30 Months, Single Words 10-15 Words. No Voluntary Sentences. Eczema, Recurrent Ear Infections.
Insulin uIU/mL
1.31
47.16
43.99
Glucose mg/dL
64
127
150
Autism Case 8 . Insulin And Glucose Profiles  of  A 7-Yr-Old Boy Presenting With Diagnoses of Autism, Inhalant Eczema, Food Allergy, and History of Multiple Courses of Antibiotics for Sore Throats.
Insulin uIU/mL
11.0
Glucose mg/dL
73
Autism Case 9. Insulin And Glucose Profiles  of A Six-Yr-Old Boy Presented With Autism, Hypothyroidism, Food and Inhalant Allergy.
Insulin uIU/mL
13.0
Glucose mg/dL
85
The staff of a university hospital mishandled the blood samples on two different occasions.
Autism Case 10. Insulin and Glucose Profile of A 28-yr-old Man Who Was Diagnosed With Autism with complete Absence of Expressive Speech Until Age 4 And Then Transitioned to Asperger’s Syndrome. At Age 21, He Was An Excellent Athlete But Could Speak Only To His Mother.
Insulin uIU/mL
7
174
365
71.9
7.9
Glucose mg/dL
81
178
160
85
56
Follow-Up Testing One Year Later
Insulin uIU/mL
8.2
139.9
152.0
40.82
2.82
Glucose mg/dL
88
128
125
100
47

Free-Access Library for Reversing Diabetes.

First things first: Only you can reverse your diabetes, not anyone else.

What Comes First Rising Blood Sugar Level, Or Rising Blood Insulin Level?

 

Majid Ali, M.D.

No question is more important for stemming the global tides of insulin toxicity and diabetes than the question in the title.

(Part of the Diabetes Question Series)


 

The Answer:

Insulin levels rise first, usually by five, ten, or more years before blood sugars level rise.

Why is this important?

Because insulin toxicity continues to cause cellular damage in the liver, kidneys, heart, brain, eyes and other organs unknown to the patient and the doctor if insulin tests are not done.


 

Citations for the Diabetes Question Series

MAJID ALI, M.D.

Free Access Library of Articles for Reversing Hyperinsulinism and Type 2 Diabetes

(Part of the Diabetes Question Series)


References 
1.     M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit Disorders. Townsend Letter for Doctors and Patients. 2004;253:64-65.
2.     Ali M. Oxygen and Aging. Book Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000. .
3.     Ali M. Succinate Retention. In: Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–435.
4.     Ali M. Succinate Retention: The Core Krebs Dysfunction in Immune-Inflammatory Disorders. Townsend Letter. 2015;388:84-85.
5.     Ali M. Epidemic of Dysoxygenosis and the Metabolic Syndrome. In: The Principles and Practice of Integrative Medicine. Volume 5. Pp 246-256. Canary 21 Press. New York. 2005.
6.     Ali M. Dysox and Climatic Chaos –  The primacy of oxygen issues over carbon issues. Part I. Townsend Letter-The examiner of Alternative Medicine. 2008;299:125-132.
7.     Ali M. Oxygen, Insulin Toxicity, Inflammation, And  the Clinical Benefits of Chelation. Part I. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.
8.     Ali M. Insulin Reduction and EDTA Chelation: Two Potent and Complementary Approaches For Preventing and Reversing Coronary Disease. Oxygen, Insulin Toxicity, Inflammation, and the  Clinical Benefits of Chelation – Part II. Townsend Letter-The examiner of Alternative Medicine. 2010;323:74-79. June 2010.
9.     Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.
10. Ali M. Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
11. Ali M. Importance of Subtyping Diabetes Type 2 Into Diabetes Type 2A and Diabetes Type 2B. Townsend Letter-The Examiner of Alternative Medicine. 2014; 369:56-58.
12. Ali M. Dasoju S, Karim N, Amin J, Chaudary D. Study of Responses to Carbohydrates and Non-carbohydrate Challenges In Insulin-Based Care of Metabolic Disorders.  Townsend Letter-The Examiner of Alternative Medicine. 2016; 391:48-51.
13. Ali M, Fayemi AO, Ali O. Dasoju S, et al. Shifting Focus From Glycemic Status to Insulin Homeostasis. .  Townsend Letter-The Examiner of Alternative Medicine. 2017;402:91-96.
14. Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic Description: eta cells through GPR40Nature;422:173–176.
15. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
16. Reaven GM, Hollenbeck C, Jeng CY, et al. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDMDiabetes. 1988;371020–1024.
17. Sako, Y. & Grill, V. E. A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidationEndocrinology 127, 1580–1589 (1990). |
18. Rhodes, C. J. Type 2 diabetes — a matter of Description: eta-cell life and death? Science. 2005;307:380–384.
19. Kahn, S. E., Bergman, R. N., Schwartz, M. W., Taborsky, G. J. & Porte, D. Short-term hyperglycemia and hyperinsulinemia improve insulin action but do not alter glucose action in normal humansAm. J. Physiol.1992;262:E518–E523.
20. Ali  M. Molecular Basis of Autism and Dysuatonomia – The Impeded Progenitor Cell Progression (IPCP) model of ASD and Dysautonomia.  Townsend Letter for Doctors and Patients. 2017 (In press)
21. Ali  M.  Insulin Laboratory Ranges. https://alidiabetes.org/2016/02/25/insulin-laboratory-ranges/
22. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116 :1793B1801.
23. Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.
24. International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. www.diabetesatlas.org.
25. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
26. Steven S, Hollingsworth KG, Al-Mrabeh A, et al. Very-Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiologic Changes in Responders and Nonresponders. Diabetes Care. 2016 Mar 21. pii: dc151942.
27. Tilman D, Clark M. Global diets link environmental sustainability and human health. Nature. 2014;515, 518B522.
28. Hu, F. B. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care. 2011; 34:1249B1257.
29. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116 :1793B1801.
30. Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.
31. International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. www.diabetesatlas.org.
32. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
33. Ali M. The Principles and Practice of Integrative Medicine Volume X: Darwin, Oxygen Homeostasis, and  Oxystatic Therapies.  3 rd. Edi. (2009) New York. Institute of Integrative Medicine Press.
34. Ali M. The Principles and Practice of Integrative Medicine Volume  XI: Darwin, Dysox, and Disease. 2000. 3rd. Edi. 2008. New York.  (2009) Institute of Integrative Medicine Press.
35. Ali M. The Principles and Practice of Integrative Medicine Volume  XII: Darwin, Dysox, and Integrative Protocols. New York (2009). Institute of Integrative Medicine Press.
36. Ali M. Oxygen, Inflammation, and Castor-Cise Liver Detox. Hormones. Townsend Letter-The examiner of Alternative Medicine. 2007. Published online. http://www.townsendletter.com/Dec2007/oxygen1207.htm
37. Ali  M. Philosophy and Science of holism in healing. APPNA Journal. 2015.
38. Ali M. Hyperinsulinism Associated With Breast and Prostate Cancer. Townsend Letter-The Examiner of Alternative Medicine. 2017;402:91-96.
39. Kamada N, Seo S-U, Zhiming C, et al. Role of the gut microbiota in immunity and inflammatory disease. Nature Reviews Immunology. 2013;12:321-335.
40. Grocott M, Richardson A, Montgomery H, et a. Caudwell Xtreme Everest: a field study of human adaptation to hypoxia. Critical care 2007;11:151.
41. Bahi-Buisson N, Roze E, Dionisi C, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50:945-9.
42. Stanley SA, Kelly L, Kaasmashri N, et al. Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature. 2016  531:647–650.
43. Murphy KG, Bloom SR. Gut hormones and the regulation of energy bhomeostasis. Nature. 2006;444:854-859.

 

Link to Am Important Article

Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes

by
Majid Ali, MD, FRCS (Eng), FACP; Alfred O. Fayemi, MD, MSc (Path), FCAP; Omar Ali, MD, FACC; Sabitha Dasoju, MB, BS; Daawar Chaudhary; Sophia Hameedi; Jai Amin; Kadin Ali; Benjamin Svoboda

http://www.townsendletter.com/Jan2017/insulin0117.html

 


Hyperinsulinism Associated With Breast and Prostate Cancer

Majid Ali, M.D.

Published in the Journal Townsend Letter (2017;409:66-69

(August 2017)


 

Hyperinsulinism fans the fire of cancer. In this article, I present case studies to show diet and integrative therapies can restore insulin homeostasis and, thereby:

  1. Reduce the risk of prostate and breast cancer growth.
  2. Improve results in the treatments of these cancer.

Two Dimensions of Insulin Dysregulation

 

An Essay Competition Article
By
Aliza Durrani
Age 13
Cherry Hill, New Jersey
7/19/17

 

In the article written by Doctor Majid Ali I have learned that Type 1 diabetes can’t get reversed while Type 2 can. This happens because Type 1 DM produces none to very little insulin while type 2  DM produces either a lot of insulin which does not work due to resistance or produce little to none insulin because their pancreas is failing after not being treated. In the article I agree with the author when he says we should be checking insulin level early on. In routine practice I am shocked that we don’t check insulin level and we only check glucose level. As a 13 year old that is a no brainer to me. If we check insulin level early on we can reverse the type 2 diabetes and since we only check glucose level this can cause people to go years to decades without being treated, resulting by the pancreas to burn out.


Insulin Diet, Insulin Detox, and Insulin Dysox

In the article I have learned that the glucose and insulin levels should be going down at the 2 hour mark in someone’s body who is not diabetic, but in the table the information is reported for a 75 year old women and it shows the glucose level and insulin level escalating each hour and not going down at the 2-3 hour mark, which means the person is diabetic and is insulin resistant. After the patient had completed a successful 3D protocol including diet, detox,and dysoxic comorbidities the last test taken on the graph was April 14, 2015 the test results appear to be normal because the levels were controlled and went down at the 2-3 hour mark resulting to her diabetes to be reversed. Also I have gained knowledge about Hyperinsulinism, it causes inflammation to organs, which can cause cancer, strokes,heart attack, etc. Hyperinsulinism is the pancreatic response to increased energy requirement to repair the injured tissue.


Two Dimensions of Insulin Dysregulation

Lastly I have learned that insulin dysregulation has two dimensions the first one is pathophysiology of hyperinsulinism(predates Type 2 DM and is not accompanied by glycemic),and the last one is dimension of T2D(accompanied by hyperglycemia). This article has given me a lot of knowledge and gives me a new look into the medical field. Studies like this will help the future to find cures for other medical issues.

What Might APPNA Contribute to Controlling Diabetes pandemic?

Majid Ali, M.D.

FRCS (Eng), FACP (Path)

Soul Author of The Principles and Practice of Integrative Medicine (12 Volumes) 


 

The author is available for personal communication concerning this paper with interested APPNA clinicians by phone at 212-873-2444 or by e-mail at askipm@aol.com.


The author’s work in molecular biology of oxygen1-6and molecular biology of insulin7-12 led him to recognize a need for a shift of focus from glycemic status to insulin homeostasis (the “Shift”).13,14 Here he marshals strong basic science and epidemiological lines of evidence for the Shift (Tables 1-3), and  presents robust reasons for suggesting that  APPNA,  a dedicated physician community, consider a long-term organizational  initiative to contribute efforts to stem global tides of hyperinsulinism which predates Type 2 diabetes (T2D) by five,  ten, or more years.

During the years of hyperinsulinism-to-T2D progression, cellular populations in nearly all body organs suffer diffuse and incremental damage inflicted by undetected and unmanaged non-metabolic toxicity of insulin dysregulation. Notable among them are disorders of neurodevelopment (autism and dysautonomia15,16), blindness from insulin-induced optic neuritis,13 mitochondrial dysfunction,1,13 immune-inflammatory entities,13 endothelial dysfunction,17 vagus nerve dysfunction,18 persistent cellular repair response (after chemotherapy for cancer,19 for instance), and hepatic lesions (such as steatosis). In his broader oxygen-insulin perspective of hyperinsulinism8 the author recognizes hyperinsulinism as chronic energetic response to increased energy requirements of cellular repair processes.

It is noteworthy that all clinical and laboratory work done for the above-cited publications was completed without any private or government funding. The same held for author’s related works in molecular and cellular pathology, as well as in therapeutics in the fields of environmental medicine, clinical nutrition, and immune-inflammatory disorders in the holistic-integrative models presented in the 10th, 11th, and 12thvolumes of The Principles and Practice of Integrative Medicine.20-22

Insulin Homeostasis Protocol

The central goal of the proposed “Insulin Homeostasis Protocol” (the “Protocol”) is for APPNA to develop and implement a long-term organizational plan for shifting focus from glycemic status to insulin homeostasis in order to: (1) improve clinical outcome of individual patients with integrative treatments: (2) simplify patient education for superior compliance; (3) build an organizational insulin database for ongoing studies of the non-metabolic and metabolic consequences of disrupted insulin homeostasis; (4) document the prevalence and patterns of progression of hyperinsulinism co-morbidities, including T2D; (5) gather clinical data for examining the efficacy of indigenous therapies; and (6) foster the science and philosophy of holism in healing.

The Protocol is designed to be an all-voluntary distance-learning (internet-based) program. No need for significant outside funding is anticipated for APPNA participating clinicians; the initial time commitment of the APPNA administrative staff is expected to be modest.

Notable Strengths of the Protocol

The Protocol has some especial strength.   Notable among them are: (1) enhanced clinical results for individual patients (extensively documented in the author’s Darwin and Dysox Trilogy20-22 and multiple case studies presented in this article); (2) no-cost internet-based distance learning for participating APPNA clinicians; (3) no clinical restrictions on the participants in the integrative model  of the dietary, detox, and lifestyle Protocol guidelines; (4) no restrictions on concurrent use of pharmacologic regimens; (5) simplicity and uniformity of record keeping format for the insulin database for publications (illustrated in Tables used for presenting ; (6) no need for contractual obligations for APPNA, nor for APPNA clinicians; and (7) no additional uncovered cost of initial post-glucose challenge insulin and glucose profiles, and limited follow-up yearly insulin tests  (as has been the case for the author and his colleagues).

Type 2 diabetes is a spreading pandemic. In 2013, China in a large national study reported a prevalence rate of prediabetes and Type 2 diabetes (T2D) (50.1% of adults).1 In 2017, the author and his colleagues reported a prevalence rate of hyperinsulinism of 75.1% in  a survey of post-glucose challenge insulin and glucose profiles in 684 subjects in New York metropolitan area.13 This, to the authors’ knowledge, was the first statistical documentation of hyperinsulinism-to-T2D progression with direct measurements of blood insulin and glucose concentrations with multiple timed blood samples following a 75-gram glucose challenge.  The much higher rate of hyperinsulinism (75.1%) in New York population than the prevalence of prediabetes and T2D among the Chinese (50.1%) is not surprising since tests for the glycemic status provide only indirect information concerning the underlying insulin dysregulation.

In the 201713 and earlier reports,7-12 the author and his colleagues explored the following questions: (1) How does insulin resistance begin; (2) What is optimal insulin homeostasis; (3)  What is the prevalence of hyperinsulinism in a general population of New York metropolitan area; (4) What are the patterns of progression and/or arrest of hyperinsulinism-to-T2D continuum; (5) What are the non-metabolic developmental, differentiative, immune-inflammatory, degenerative, and metabolic effects of undetected incremental degrees of insulin dysfunction; (6) How do the diagnostic efficiencies for T2D of post-glucose challenge and insulin responses compare with those of the standard glucose tolerance; (7) How does insulin-based hyperinsulinism modification and T2D reversal plan compare with those based on glycemic criteria, especially in the cases of gestational diabetes and large-sized babies; and (8) What might be the crucial clinical entities in which unmasked hyperinsulinism poses special hazards, i.e., autism, Asperger’s syndrome, pediatric dysautonomia, childhood weight gain and obesity, pediatric fatty liver, peripheral neuropathy,  drug-induced tissue repair responses (during chemotherapy for cancer, for instance), polycystic ovarian syndrome, pustular  acne, and diverse allergic and chronic immune-inflammatory disorders.

Insulin Dysregulation in Chronic Cellular Repair Responses

All repair mechanisms in the body have  expanded energy requirement demands. Insulin can be rightfully considered the master energy hormone of the body. From an evolutionary energetic perspective, the lowest blood insulin concentrations accompanied by unimpaired glucose tolerance have been designated optimal insulin homeostasis  (Table 1).  Table 2 showing the correlation of incremental glycemic changes sheds light on the hyperinsulinism-T2D continuum. Our article entitled “Shifting Focus From Glycemic Status to Insulin Homeostasis is posted in full at www.alidiabetes.org, and furnishes a large body of original observations, including many of the above-cited forms of toxicity of hyperinsulinism fully referenced.

Table 1. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes
Insulin Category* Percentage of Subgroup Mean Peak Glucose  mg/dL(mmol/mL) Mean Peak Insulin (uIU/mL)
Exceptional Insulin Homeostasis    N =  12** 1.7% 110.2     (6.12) 14.3
Optimal Insulin Homeostasis            N =  126 24.9 % 121.2     (6.73) 26.7
Hyperinsulinism, Mild                         N =  197 38.9 % 136.5   (7.58) 58.5
Hyperinsulinism,  Moderate              N =  134 26.5 % 147.0    (8.16) 109.1
Hyperinsulinism,  Severe                   N =  49 9.7 % 150.0    (8.33) 231.0
#   Correlation coefficient, r value, for means of peak glucose and insulin levels in the five insulin categories is 0.84.

*Criteria for classification: (1) Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis with fasting insulin concentration of <2 uIU/mL and mean peak insulin concentration of <20; (2) optimal insulin homeostasis, peak insulin <40 accompanied by unimpaired glucose tolerance; (3) mild

Table 2. Insulin Homeostasis Categories in 178 Study Subjects With Type 2 Diabetes
Insulin Category Percentage of Subgroup Mean Peak Glucose mg/dL(mmol/mL) Mean Peak Insulin (uIU/mL)
T2D With Hyperinsulinism, Mild          N =  53 29.0% 252.0   (14.00) 55.4
T2D With Hyperinsulinism, Moderate N =  42   24.0% 242.1   (13.45) 112.4
T2D With Hyperinsulinism, Severe       N =  24 13.9% 224.6   (12.47) 298.0
T2DF With Low Insulin Levels               N =  59 33.1% 294.0    (16.33) 22.9

Reading Insulin/Glucose Profiles As Examining Surgical Pathology Slides

Within some months of beginning my study of insulin homeostasis with 3-hour post-glucose-challenge insulin and glucose profiles, I found myself reading the profiles as I read microscopic slides as a hospital surgical pathologist. One might expect that individual subjects will display wide variations in their insulin and glucose profiles in most instances. This, indeed, is the case . This point is amply demonstrated in case studies shown in Tables 3-7. Table 3 shows what is usually dismissed as an error of omitting the glucose challenge by the patient or the  lab staff since the “flat” post-glucose-challenge tolerance pattern is not a generally recognized entity. It is caused by a brisk initial insulin spike which masks the expected initial glucose spike. This can be readily proved by taking measurements at 1/2-hour post-challenge blood sample. Tables 7 documents insulin dysregulation in autism and pediatric dysautonomia.

Table 3. Optimal Insulin Homeostasis With Very Low Blood Insulin Concentrations and Unimpaired “Flat” Glucose Tolerance Curve* of A 52-Yr-Old 5’1” Woman With Constipation and Osteoarthritis.
Fasting 1-Hr 2-Hr 3-Hr
Insulin uIUi/mL <2 17 15 6
Glucose mg/mL 75 61 72 71

 

Table 4. Insulin and Glucose Profiles of 75-Yr-Old 5’7” Woman Weighing 192 lbs. Who Presented Following A Coronary Bypass Procedure With Fatigue, Sinusitis, and Without Known Type 2 Diabetes (Not An Uncommon Case In the Author’s Integrative Clinical Practice). A1c 5.6%.
6.3.2010 Fasting 1-Hr 2-Hr 3-Hr
Insulin uIUi/mL 9.8 25 92.4 2.2
 Glucose mg/mL 112 170 241 273
7.23.2013. Insulin Tests Not Ordered By Her Primary Physician. A1c 5.8%
Insulin uIUi/mL
Glucose mg/mL 97 159 219 247
5.11.2014. ”Mostly Good Compliance” By  Patient’s Account.  A1c  5.7
Insulin uIUi/mL 6.43 58.2 33.87 6.4
Glucose mg/mL 99 182 139 81
2016 Hospitalized for Angina. A1c 5.7. No Diabetic Drugs Prescribed By the Attendning Cardiologist.

 

Table 5. Reversal of Type 2 Diabetes in a 78-Yr-Old 5’2” Woman Weighing 162 Lbs. Achieved By Dramatic Hyperinsulinism Modification (Reduction of 3-Hr Insulin from 152 uIU/mL in 2013 to 75.2 in 2014 to 39.7 in 2015, indicating  restoration of Insulin Homeostasis.
4.30.2013 Fasting 1-Hr 2-Hr 3-Hr
Insulin uIUi/mL 16 59 113 152
 Glucose mg/mL 112 214 241 155
10.17.2014,   A1c  6.3%
Insulin uIUi/mL 23.8 36.9 114.7 75.2
 Glucose mg/mL 116 253 297 172
4.14.2015,  A1c 5.9%
Insulin uIUi/mL 6.2 42.9 51.2 39.7
 Glucose mg/mL 96 193 112 105

 

Table 6. Severe Hyperinsulinism In A Previously Health 13-Yr-Old Girl With Multiple Hospitalizations for Recurrent Pneumonia, Thrombocytopenia, Polyarthralgia, Polymyalgia , and Severe Optic Neuritis With Complete Loss of Vision in Right Eye. Her Final Diagnosis in the Hospital was Systemic Lupus Erythematosus*
Fasting 1Hr 2Hr 3Hr
Insulin uIU/mL 27.9 424.0 718.2 571.7
Glucose mg/mL 70 157 150 111
Insulin and Glucose Profiles Obtained After Four Months of Robust Integrative Parenteral Nutritional and Detox Therapies With Focus on Restoration of Gut Flora.
Insulin uIU/mL 7.2 238.5 208.0 132.0
Glucose mg/mL 81 181 130 97
*The patient showed dramatic improvement  in all areas except in right eye blindness. Follow-up questioning revealed a history of massive exposure to mold overgrowth while playing in an abandoned building.

Information Sources

I consider the journal Nature to be the supreme source of information in the world of science. Since 2015, Nature frequently e-published my comments expressing holistic-integrative perspective on health and healing concerning major articles published by the journal. Below are excerpts from five of those pieces on the subject of this proposal for APPNA (citations within the text are originals from e-publications):

  1. Shifting Focus From Glycemic Status to Insulin Homeostasis14

 Type 2 Diabetes (T2D) is rapidly eclipsing other chronic diseases in becoming the preeminent threat to human health worldwide…. The work of Yamaguchi and colleagues must be celebrated in this larger context. Their previous work involved generation of whole organs from donor pluripotent stem cells using their chimaera-forming ability to complement organogenesis-disabled host animals in vivo. They now report generation of autologous functional islets with interspecies organogenesis through interspecies blastocyst complementation. This stellar work advances the goal of treating diabetes with islet transplantation. Here, Yamaguchi  et al. also put forth a serious challenge to physician community: How to protect transplanted islet cells from the host elements that caused hyperinsulinism leading to Type 2 diabetes in the first place?

  1. Obesity, Energetics, Environment, and Hyperinsulinism23

Just how error-prone and self-correcting is science? Allison and colleagues raise a question that physicians often raise – in hospitals, clinics, and laboratories. A more compelling question for those interested in obesity, energetics, and inflammation, and insulin homeostasis is: How can the subjects of obesity and energetics be investigated and/or discussed without considering the tedious and disconcerting matter of environmental and inflammatory toxins that impair mitochondrial function and oxygen signaling? Automobile mechanics know well how their engines get clogged and lose efficiency and mileage. In 2004, the author published data concerning impaired mitochondrial function in chronic immune-inflammatory and metabolic disorders.1  His observations were validated by the work of others as well as his follow-up studies.23

  1. Osteocrin, Making Connections, and Autism16

Ataman et al. linked osteocrin, a gene expressed in muscles and bones, to a new primate-specific enhancer sequence that binds to a myocyte enhancer factor 2 (MEF2.) (ref. 1). MEF2C mutations resulting in haploinsufficiency represent a form of intellectual disability in humans. (ref.2,3). MEF2A- and MEF2C-binding sites are enriched in genes associated with idiopathic autism spectrum disorder (ref. 4).

This new osteocrin work is especially important for integrative clinicians who care for autism and other disorders of developmental neurobiology. No pharmacologic agents to treat autism spectrum are available at this time. However, it is well established that neuronal activity triggers distinct transcriptional responses in different neuronal subtypes (ref. 5) This offers an opening for integrative clinicians to investigate the potential benefits of non-pharmacologic approaches to enhance neuronal activity to evoke desirable neurological responses for improved clinical outcomes. Notable among these are dietary, nutritional, metabolic, and gut mircobiota-directed therapies, as well as educational and behavioral programs. Specifically, the use of injectable and oral glutathione, methylcobalamine, taurine, calcium, magnesium, vitamin B complex usually yield gratifying results in treating atism (ref. 6,7).

The work of Ataman et al inspires this writer to pursue his impeded progenitor cell progression model of autism (ref. 6). He put forth this unifying model as a frame of reference for establishing clinical priorities to improve clinical results by identifying and addressing all prenatal and postnatal challenges to developmental neurobiology which seem relevant to the pathogenesis of ASD. The core tenet of this model is impeded neuronal progenitor cell progression to mature neurons during antenatal and postnatal lives caused in autism is disrupted oxygen signaling (ref. 6,8,9) resulting from: (1) Krebs cycle dysfunction (ref. 10); (2) overdriven immune-inflammatory dynamics (ref. 11); and (3) disruptions of insulin homeostasis and IGF1-dynamics (ref. 12,13). The members of this trio amplify challenges to progenitor cell progression posed by one another, and impede progenitor cell progression during antenatal and postnatal lives.

  1. Insulin.Autism.Hypothalamus24

The work of Stanley et al. points out how their constructs targeting glucose-sensing neurons will also be applicable to other areas, including insulin signaling. I have two specific reasons for celebrating this work. First, my work with hyperinsulnism and diabetes led me to recognize a clear need for a shift of focus from glycemic status to insulin homeostasis for stemming the tide of Type 2 diabetes in children (ref. 2-4). Second, I have special interest in the subject of hyperinsulinism in children with neurological challenges, such as autism and dysautonomia. (ref.5) Readers might find the following data concerning four children with hyperinsulinism, two with autism and two with dysautonomina, interesting. The insulin and glucose profiles were obtained with blood samples drawn at fasting and 1-hour, 2-hour, and 3-hour after a 75-gram challenge. I also include an insulin profile of a healthy subject with unimpaired glucose tolerance as a control. Insulin and glucose concentrations in 3-hour insulin and glucose profiles of  four children given below are expressed in uIU/ml and mg/mL respectively.

Table 7. Insulin and Glucose Profiles of Two Children each With Autism, and Dysautonomia, and One Control Child .
Fasting 1-Hr 2-Hr 3-Hr
Autism Case 1
 Insulin uIU/mL 24.4 73.8 71.6 28
Glucose mg/mL 95 79 79 69
Autism Case  2
Insulin uIU/mL 6.2 40.3 41.5 24.8
Glucose mg/mL 96 131 109 57
Pediatric Dysautonomia Case 1
Insulin uIU/mL 9.3 90.7 119.9 53.8
Glucose mg/mL 78 165 141 99
Pediatric Dysautonomia Case 1
 Insulin uIUi/mL 3.9 49.59 13.1 7.8
Glucose mg/mL 84 96 71 77
Control Subject Without Any Neurologic Disorder
Insulin uIU/mL <2 18 4 <2
Glucose mg/mL 77 109 74 52

 

  1. Darwin Moms, Nursing Milk, and Antibiotic Resistance25

Darwin moms have much to teach clinicians like me. To cite one example, women in Punjab diligently follow the family tradition of mustard oil rubs over their bellies daily for forty days after delivering a baby. I recommend this simple remedy to my American patients who nearly always find it beneficial in improving bowel health and reducing abdominal fat. They also report good results with castor oil rubs for their colicky babies.

Darwin moms have taught me much about many other remedies for controlling pregnancy-related digestive-absorptive disruptions and for improving their nutritional,  metabolic, and immune status, as well as of their children. Such measures profoundly affect the nourishing quality and safety of nursing milk, a crucially important immune booster. This approach can be expected not only to reduce the need for antibiotics but also diminish the frequency and intensity of their adverse effects when antibiotics cannot be avoided.

APPNA and Global Challenges of Disrupted Oxygen and Insulin Signaling

In closing, APPNA has an impressive world-class “clinician capital.” What might it contribute to the daunting challenge of stemming global tides of diabetes? Hyperinsulinism is recognized not only as the primary pathogenetic  mechanism for Typ2 diabetes but also as playing central roles in  diverse developmental, diffferentiative,  immune-inflammatory,  cardiovascular, neurologic, hepatic, endocrine, and cellular repair-related pathologies. Within the broader evolutionary context, the incremental “non-metabolic effects” of disrupted insulin homeostasis inflict diffuse cellular injury in nearly all organ systems of the body. The case of a 13-yr-old with total loss of vision in one eye presented in Table 6 and those of children with autism and dysautonomia in Table 7 offer intellectual and clinical challenges worthy of APPNA physicians. The integrative clinical Protocol guidelines proposed here also harness myriad low-cost indigenous therapies. The oxygen-insulin dimensions of the Protocol provide the scientific underpinning and rationale for gauging and engaging therapeutic aspects of molecular biology of oxygen and insulin.

In this light, APPNA clinicians considering the Protocol may look forward to exploring rewarding new dimensions of the new global realities of health and healing. Excerpts from the writer’s comments published online by the journal Nature provide windows to some of these dimensions. I add here that I consider publications in Nature analogous to the U.S Supreme Court admitting cases – to be presented, argued for and against, and then to be ruled on.

References

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  2. Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014; 515:431–435.
  3. Ali M. Succinate Retention. In: Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–435. Data after references).
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  8. Ali M. Oxidative regression to primordial cellular ecology. J Integrative Medicine 1998; 2:4-55.
  9. Oxygen, Insulin Toxicity, Inflammation, and  the Clinical Benefits of Chelation. Part I. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.
  10. Ali M. Importance of Subtyping Diabetes Type 2 Into Diabetes Type 2A and Diabetes Type 2B. Townsend Letter-The Examiner of Alternative Medicine. 2014; 369:56-58.
  11. Ali M. Dasoju S, Karim N, Amin J, Chaudary D. Study of Responses to Carbohydrates and Non-carbohydrate Challenges In Insulin-Based Care of Metabolic Disorders. Townsend Letter-The Examiner of Alternative Medicine. 2016; 391:48-51.
  12. Ali M. Epidemic of Dysoxygenosis and the Metabolic Syndrome. In: The Principles and Practice of Integrative Medicine. Volume 5. Pp 246-256. Canary 21 Press. New York. 2005.
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  14. Ali M. Shifting Focus From Glycemic Status to Insulin Homeostasis. E-comments In Nature. 2017;542:191.Re: Kobayashi T, Yamaguchi T, Hamanaka S, et al. Generation of rat pancreas in mouse by interspecies blastocyt injection of pluripotent stem cells. Cell. 2010;142:787-799.
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  19. Ali M. Cancer,-Endothelium Dynamics, and DR6-Based Anti-Metaststic Therapies. Comments e-published in: 2016;536:215-218.
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  24. Ali M. Autism.Hypothalamus. e-published at www.Nature.com. In: Nature. 2016;531:647-650.
  25. Ali M. Darwin Moms , Nursing Milk, and Antibiotic Resistance. E-published at Nature.com. 533:212.

END Protocol

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